Purpose: Krüppel-like factor 4 (KLF4) promotes corneal epithelial (CE) cell fate while suppressing mesenchymal properties. TGF-β plays a crucial role in cell differentiation and development, and if dysregulated, it induces epithelial-mesenchymal transition (EMT). As KLF4 and TGF-β regulate each other in a context-dependent manner, we evaluated the role of the crosstalk between KLF4 and TGF-β-signaling in CE homeostasis. Methods: We used spatiotemporally regulated ablation of Klf4 within the adult mouse CE in ternary transgenic Klf4Δ/ΔCE (Klf4LoxP/LoxP/ Krt12rtTA/rtTA/ Tet-O-Cre) mice and short hairpin RNA (shRNA)-mediated knockdown or lentiviral vector-mediated overexpression of KLF4 in human corneal limbal epithelial (HCLE) cells to evaluate the crosstalk between KLF4 and TGF-β-signaling components...

BACKGROUND/AIMS: Reversible unilateral ureteral obstruction (R-UUO) is a model of renal injury used to study the structural and functional recovery of the kidneys after relief of the obstruction. This model has a prominent potential for the study of inflammatory and immune processes, cellular and tissue regeneration. Here we sought to describe a model of renal injury and repair R-UUO in mice. METHODS: Eight week-old C57BL/6J male mice were divided into 5 groups (n = 5 each): UUO day 1, 2, 3, 4 and 5...

BACKGROUND: The (pro)renin receptor [(P)RR)] is involved in the activation of local renin-angiotensin system and subsequent development of cardiovascular disease. We investigated the therapeutic effect of a (P)RR blocker, handle region peptide (HRP), on chronic kidney disease (CKD)-associated heart failure. METHODS AND RESULTS: CKD was induced in C57BL/6J mice by 5/6 nephrectomy. Eight weeks later, cardiac dysfunction and cardiac dilatation with hypertension developed...

Due to recent advances in research on mesenchymal stem cells (MSCs), MSCs are expected to be used in various clinical applications. However, securing adequate cadaveric donors and safety of living donors are major issues. To solve such issues, we have examined to develop clinical grade neonatal porcine bone marrow-derived MSCs (npBM-MSCs). Clinical grade neonatal porcine bone marrow cells were collected, frozen, and sent to our laboratory by air. The npBM-MSCs were isolated from thawed bone marrow cells, then frozen...

Systemic sclerosis is a connective tissue disease characterized by tissue fibrosis leading to interstitial lung disease. Transforming growth factor-β (TGF-β) has been of interest as a potential diagnostic marker and also as a drug target in systemic sclerosis. The aim of this study was to assess the serum content of TGF-β1 in patients with systemic sclerosis and to assess its potential role in tissue fibrosis. The study included 30 patients, 5 men and 25 women, of the mean age of 46.9 ± 12.8 years, diagnosed with systemic sclerosis...

Water is the most important nutrient in animal nutrition; however, water intake is rarely measured. The objective of this study was to determine whether previously published water intake (WI) equations for beef cattle would accurately predict WI from four experiments conducted under tropical conditions. The experiments were conducted from 2013 to 2015. Nellore (Bos indicus) growing bulls (Exps. 1, 2, and 3) and heifers (Exp. 4) were used in the feedlot trials. In all experiments, animals were fed for ad libitum DMI...

Activation of hepatic stellate cells by free radicals is an initial step in the development of liver fibrosis. Zataria multiflora Boiss (ZM) essential oil as a natural product has antioxidant activity and maybe a suitable candidate for treatment or prevention of the disease. Thus, this study aims to evaluate the protective effect of ZM oil in CCl4 induced liver fibrosis. Male rats were divided into 5 groups, group C: control rats; CO: vehicle control group; CE: rats that received essential oil (500 µl/kg); F: fibrosis group, rat were intraperitoneally injected with CCl4 (1 mL/kg); FE: fibrosis rats that received both CCl4 and ZM essential oil as mentioned above...

PROBLEM: Osteoarthritis (OA) is a chronic disease with a very high incidence and the pathology of which is quite complex. Epidemiological investigation showed that OA may be related to smoking and estrogen levels, but there are few studies focused on the cross-effect of these two factors. This research aims to investigate the molecular mechanism of nicotine and estrogen effects on chondrocytes to study the effect of smoking on the incidence of osteoarthritis in women. METHOD OF THE STUDY: Nicotine was added to obtain inflammatory supernatants of macrophages, which were used to induce chondrocyte inflammation...

Background: Periostin has been shown to be upregulated in chronic rhinosinusitis with nasal polyps (CRSwNP), especially in the CRSwNP patients with asthma. However, the underlying mechanism that how periostin contributes to the polyp genesis remains unclear. Methods: In this study, we collected 63 CRSwNP patients' nasal polyps (NPs) and 25 control subjects' uncinated tissues. The expressions of periostin, thymic stromal lymphopoietin (TSLP), and other proinflammatory cytokines were examined using IHC staining, qRT-PCR, Western blot (WB), ELISA and FACS...

PURPOSE: The leukocyte- and platelet-rich fibrin block (L-PRF block) is a composite graft that combines a xenograft that is acting as a scaffold with L-PRF membranes that serve as a bioactive nodule with osteoinductive capacity. This study evaluated the properties of the L-PRF block and its components in terms of release of growth factors, cellular content, and structure. MATERIALS AND METHODS: The concentration of transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), platelet-derived growth factor-AB (PDGF-AB) and bone morphogenetic protein-1 (BMP-1) released by a L-PRF membrane (mb) and a L-PRF block were examined with ELISA for five time intervals (0 to 4 hours, 4 hours to 1 day, 1 to 3 days, 3 to 7 days, 7 to 14 days)...

Umbelliferone (UMB) is a natural coumarin that has diverse biological activities. However, its potential to protect against liver fibrosis has not been reported yet. This study aimed to investigate the protective effect of UMB against carbon tetrachloride (CCl4 )-induced liver fibrosis in rats. Rats received CCl4 and UMB for 8 weeks and samples were collected for analyses. CCl4 induced a significant increase in serum levels of liver function markers and pro-inflammatory cytokines. Treatment with UMB significantly ameliorated liver function markers and pro-inflammatory cytokines and prevented CCl4 -induced histological alterations...

BACKGROUND: Fetal origin of adult cardiovascular disease is one of the most pressing public concerns and economic problem in modern life. Maternal cigarette smoking/nicotine abuse increases the risk of cardiovascular disease in offspring. However, the underlying mechanisms and theranostics remain unclear. We hypothesized that fetal and neonatal nicotine exposure enhances microRNA-181a (miR-181a) which targets large-conductance Ca2+ -activated K+ (BKCa ) channels, resulting in increased coronary vascular tone in adult offspring...

The most epidemic liver disorder non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis and inflammation with hepatocellular damage. Recently, it is predictable to be the extensive cause for liver transplantation. The absence of an approved therapeutic agent for NASH is the reason for investigating saroglitazar (SAR) which showed promising effects as a dual PPAR-α/γ agonist in recent studies on NASH. Here, we aimed to investigate the effect of SAR on NASH induced in rats by the administration of high-fat emulsion (HFE) and small doses of lipopolysaccharides (LPS) for 5 weeks...

Recent research into the cancer stem cell (CSC) concept has driven progress in the understanding of cancer biology and has revealed promising CSC-specific targets with regard to drug discovery. As malignancies of lung cancer have been shown to be strongly associated with activities of CSCs, we examined the effects of Ti0.8O2 nanosheets on these cells. Here we show that the nanosheets target lung CSCs, but not normal primary dermal papilla (DP) stem cells. Whilst Ti0. 8O2 caused a dramatic apoptosis along with a decrease in CSC phenotypes, such nanosheets minimally affected those aspects in primary human DP cells...

Hepatic fibrosis is chronic liver damage with many causes that has a relatively high death rate. The current study showed that lncRNA GAS5, miR-23a and PTEN play important roles in the pathological process of hepatic fibrosis but have a relatively unclear regulatory mechanism. This study aimed to investigate the roles of lncRNA GAS5, miR-23a and PTEN in the pathological process of hepatic fibrosis and HSC activation. We used CCl4 intraperitoneal injections to establish a rat hepatic fibrosis model and exogenous TGF-β1 to establish a hepatic stellate cell (HSC) activation model...

Background: Despite intensive research, regeneration of articular cartilage largely remains an unresolved medical concern as the clinically available modalities still suffer from long-term inconsistent data, relatively high failure rates and high prices of more promising approaches, such as cell therapy. In the present study, we aimed to evaluate the feasibility and long-term efficacy of a bilayered injectable acellular affinity-binding alginate hydrogel in a large animal model of osteochondral defects...

Metoprolol {systematic name: (RS)-1-isopropylamino-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol}, C15 H25 NO3 , is a cardioselective β1 -adrenergic blocking agent that shares part of its molecular skeleton with a large number of other β-blockers. Results from its solid-state characterization by single-crystal and variable-temperature powder X-ray diffraction and differential scanning calorimetry are presented. Its molecular and crystal arrangements have been further investigated by molecular modelling, by a Cambridge Structural Database (CSD) survey and by Hirshfeld surface analysis...

Objective: The aim of the current study was to investigate the protective effect of Yangyin Yiqi Mixture (YYYQ) on Bleomycin-induced pulmonary fibrosis in rats based on TGF- β 1/Smad signal pathway and epithelial to mesenchymal transition (EMT). Methods: 120 Wistar rats were randomly divided into six groups: control group, BLM group, BLM + Pred group, BLM+YYYQ-L group, BLM+YYYQ-M group, and BLM+YYYQ-H group. Rats were given an intratracheal instillation of 3 mg/kg BLM to establish the pulmonary fibrosis model and followed by different dosages of YYYQ (11, 22, 44g/kg, via intragastric gavage) or prednisone soluble (4...

Background: Studies implicate that Ang1-7 imparts protective effects in the kidney. However, its relevance in hypertensive kidney disease is not fully understood. The purpose of this study is to explore the role of Ang1-7 on renal damage/remodeling during hypertension and its potential underlying molecular-cellular mechanisms. Methods: Hypertension was induced in adult Sprague Dawley rats by infusion of ALDO (0.75μg/h) for 4 weeks with or without co-treatment of Ang1-7 (1mg/kg/day)...